Comparative genomics tools have become widely used by biologists and genomicists seeking to understand the functional regions of the human and other genomes. This proposal aims to create an integrated, easy-to-use comparative genomics package that will run on a biologist's personal machine or small cluster, allowing biomedical researchers to study genomes of interest even if they are not available through any of the major genome browsers. The package will be based on two of the most successful programs for comparative genome analysis, the VISTA Genome Browser and the LAGAN Alignment Toolkit, previously developed in our group and already used by thousands of investigators. This proposal seeks support to create a stable stand-alone software system, based on improvements and modifications to our current tools, which a researcher could use in his own laboratory, without being required to upload data to any server or use pre-computed whole genome alignments. This package will incorporate the advanced alignment and exploratory visualization algorithms already prototyped in our group. This system will give the scientist a remarkable combination of flexibility for choosing parameters, easy automation of the computation of large datasets, and privacy for their data, together resulting in the significant novel ability to closely analyze either individual genes or whole genomes. Improved VISTA/LAGAN tools will allow for enhanced use of comparative genomics for deciphering biomedically relevant features in the human genome. The target users of these resources will continue to be biomedical researchers, and thus focus will be placed on generating tools and databases that will be easy to use with readily interpretable results.